1. Technical Field
The present invention relates generally to fluid dynamics. More specifically, the invention relates to apparatus for mixing fluids, and methods of making and using such apparatus.
2. Background Art
A micromixer is a device used to mix small volumes of fluids flowing in very narrow channels. A micromixer is essential in many of the microfluidics systems targeted for use in biochemical analysis, drug delivery, and sequencing or synthesis of nucleic acids. Biological processes such as cell activation, enzyme reactions, and protein folding often involve reactions that require mixing of reactants for initiation. Mixing is also necessary in many microfabricated chemical systems that carry out complex chemical synthesis. See “Passive Mixing in a Three-Dimensional Serpentine Microchannel,” R. H. Liu, M. A. Stremler, K. V. Sharp, M. G. Olsen, J. G. Santiago, R. J. Adrain, H. Aref, and D. J. Beebe, Journal of Microelectromechanical Systems, Vol. 9, No. 2, June 2000.
When fluids flow in channels approximately the size of a human hair, the phenomenon, known as laminar flow, exhibits very different properties than fluids flowing within the macro world. Laminar flow, also associated with low Reynolds numbers, will allow the movement of different layers of the fluid and particles next to each other in a channel with little or no mixing, except for diffusion.
As explained by Liu et al., using a classification that is adapted here, micromixers can be classified as either active or passive. Passive stirring schemes include simple in-plane lamination and chaotic advection stirring (defined by Liu et al. as the rapid distortion and elongation of material interfaces). Active mixers have moving parts or externally applied forcing functions such as pressure, electric field, or ultrasound. Passive mixers typically use channel geometry to increase the interfacial area between the liquids to be mixed, thus improving the odds for diffusional mixing. These mixers can be categorized into two subclasses: in-plane mixers, which divide and mix streams within a fluid network confined to one level, and out-of-plane or lamination mixers, which use three-dimensional channel geometries. The above-referenced Liu et al. article describes a three-dimensional serpentine channel out-of-plane passive mixer, which relies on chaotic advection, as well as two in-plane mixers: square-wave channel, and straight channel. The simplest in-plane mixers merge two fluid streams into a single channel and accomplish mixing by molecular diffusion, relying on time and high diffusion coefficients to mix the fluids or move solutes between fluids. This is troublesome for biologic samples, whose constituent molecules are frequently complex oligomeric or polymeric structures. Out-of-plane, lamination mixers sequentially split and stack fluid streams in a three-dimensional fluidic network. Lamination mixers typically require multi-layer microfabrication techniques, which make them less attractive to bioanalysis system designers where targets are simple fabrication, planar designs, and ease of integation into microfluidic systems.
Several other microfluidic devices have been developed recently which attempt to improve fluid mixing within microscale devices. U.S. Pat. No. 6,136,272, which issued on Oct. 24, 2000, and is assigned to the University of Washington, describes a device for rapidly joining and splitting fluid layers within microfluidic channels which allow for diffusional mixing in two directions, in the depth direction and in the width direction. Unfortunately, the devices described in this patent, which refer to curved bridge channels used in “mixing mode,” do not describe centrifugal mixing in these channels, and in fact appear to be devoted to keeping the laminar flow streams separated in the bridge channels. The only mixing occurring in these devices appears to be in parallel, straight channels downstream from any curved bridge channel.
Patent Cooperation Treaty WO 01/89675 A2, published Nov. 29, 2001 and assigned to Micronics, Inc., describes a jet vortex mixer, generally circular-shaped, containing no moving parts, and capable of mixing both serial and laminar flow streams. This device may be termed an active mixer, in that the inlets of this device are connected with pumping valves that provide the power to the mixer and transport fluids forward and backward inside the mixer. The device requires converging sections for the fluid entering the device, thereby increasing linear velocity of the fluid prior to entering the mixing chamber. These converging sections may lead to difficulties in cleaning the device for repeated use.
U.S. Published Patent Application No. 2002/0097632 A1, published Jul. 25, 2002, describes microsystem platforms for achieving efficient mixing of one or a plurality of fluids on the surface of the platform when fluid flow is motivated by centripetal force produced by rotation, similar to a CD-ROM disc. These devices appear to be able to mix fluids only in serial fashion, not in laminar layers.
Despite recent advances, there is an unmet need in many arts for efficient, reliable, and repeatable mixing of reagents or reagents and samples in microfluidic devices. For example, biochemical analysis, drug delivery, sequencing or synthesis of nucleic acids, biological processes such as cell activation, enzyme reactions, and protein folding often involve reactions that require mixing of reactants in microspace for initiation. Mixing is also necessary in many microfabricated chemical systems that carry out complex chemical synthesis, such as combinatorial chemistry.